scholarly journals Early Mitochondrial Adaptations in Skeletal Muscle to Diet-Induced Obesity Are Strain Dependent and Determine Oxidative Stress and Energy Expenditure But Not Insulin Sensitivity

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2677-2688 ◽  
Author(s):  
Sihem Boudina ◽  
Sandra Sena ◽  
Crystal Sloan ◽  
Ali Tebbi ◽  
Yong Hwan Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Diet Induced Obesity ◽  
Strain Dependent ◽  
Mitochondrial Adaptations

scholarly journals Selenoprotein W deficiency does not affect oxidative stress and insulin sensitivity in the skeletal muscle of high-fat diet-fed obese mice

2019 ◽  
Vol 317 (6) ◽  
pp. C1172-C1182 ◽  
Author(s):  
Min-Gyeong Shin ◽  
Hye-Na Cha ◽  
Soyoung Park ◽  
Yong-Woon Kim ◽  
Jong-Yeon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Control Diet ◽  
In Vivo Studies ◽  
Selenoprotein W ◽  
Obese Mice ◽  
High Fat

Selenoprotein W (SelW) is a selenium-containing protein with a redox motif found abundantly in the skeletal muscle of rodents. Previous in vitro studies suggest that SelW plays an antioxidant role; however, relatively few in vivo studies have addressed the antioxidant role of SelW. Since oxidative stress is a causative factor for the development of insulin resistance in obese subjects, we hypothesized that if SelW plays a role as an antioxidant, SelW deficiency could aggravate the oxidative stress and insulin resistance caused by a high-fat diet. SelW deficiency did not affect insulin sensitivity and H2O2 levels in the skeletal muscle of control diet-fed mice. SelW levels in the skeletal muscle were decreased by high-fat diet feeding for 12 wk. High-fat diet induced obesity and insulin resistance and increased the levels of H2O2 and oxidative stress makers, which were not affected by SelW deficiency. High-fat diet feeding increased the expression of antioxidant enzymes; however, SelW deficiency did not affect the expression levels of antioxidants. These results suggest that SelW does not play a protective role against oxidative stress and insulin resistance in the skeletal muscle of high-fat diet-fed obese mice.

scholarly journals Cafeteria diet inhibits insulin clearance by reduced insulin-degrading enzyme expression and mRNA splicing

2013 ◽  
Vol 219 (2) ◽  
pp. 173-182 ◽  
Author(s):  
P Brandimarti ◽  
J M Costa-Júnior ◽  
S M Ferreira ◽  
A O Protzek ◽  
G J Santos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Secretion ◽  
Alternative Splicing ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Insulin Clearance ◽  
Cafeteria Diet ◽  
Mrna Levels ◽  
Insulin Degrading Enzyme ◽  
Diet Induced Obesity

Insulin clearance plays a major role in glucose homeostasis and insulin sensitivity in physiological and/or pathological conditions, such as obesity-induced type 2 diabetes as well as diet-induced obesity. The aim of the present work was to evaluate cafeteria diet-induced obesity-induced changes in insulin clearance and to explain the mechanisms underlying these possible changes. Female Swiss mice were fed either a standard chow diet (CTL) or a cafeteria diet (CAF) for 8 weeks, after which we performed glucose tolerance tests, insulin tolerance tests, insulin dynamics, and insulin clearance tests. We then isolated pancreatic islets for ex vivo glucose-stimulated insulin secretion as well as liver, gastrocnemius, visceral adipose tissue, and hypothalamus for subsequent protein analysis by western blot and determination of mRNA levels by real-time RT-PCR. The cafeteria diet induced insulin resistance, glucose intolerance, and increased insulin secretion and total insulin content. More importantly, mice that were fed a cafeteria diet demonstrated reduced insulin clearance and decay rate as well as reduced insulin-degrading enzyme (IDE) protein and mRNA levels in liver and skeletal muscle compared with the control animals. Furthermore, the cafeteria diet reduced IDE expression and alternative splicing in the liver and skeletal muscle of mice. In conclusion, a cafeteria diet impairs glucose homeostasis by reducing insulin sensitivity, but it also reduces insulin clearance by reducing IDE expression and alternative splicing in mouse liver; however, whether this mechanism contributes to the glucose intolerance or helps to ameliorate it remains unclear.

scholarly journals Defining the contribution of skeletal muscle pyruvate dehydrogenase α1 to exercise performance and insulin action

2018 ◽  
Vol 315 (5) ◽  
pp. E1034-E1045 ◽  
Author(s):  
Kristoffer Svensson ◽  
Jessica R. Dent ◽  
Shahriar Tahvilian ◽  
Vitor F. Martins ◽  
Abha Sathe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Exercise Performance ◽  
Pyruvate Dehydrogenase ◽  
High Intensity ◽  
High Intensity Exercise ◽  
Low Intensity ◽  
Low Intensity Exercise ◽  
Muscle Contractile

The pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA and is an important control point for carbohydrate (CHO) oxidation. However, the importance of the PDC and CHO oxidation to muscle metabolism and exercise performance, particularly during prolonged or high-intensity exercise, has not been fully defined especially in mature skeletal muscle. To this end, we determined whether skeletal muscle-specific loss of pyruvate dehydrogenase alpha 1 ( Pdha1), which is a critical subunit of the PDC, impacts resting energy metabolism, exercise performance, or metabolic adaptation to high-fat diet (HFD) feeding. For this, we generated a tamoxifen (TMX)-inducible Pdha1 knockout (PDHmKO) mouse, in which PDC activity is temporally and specifically ablated in adult skeletal muscle. We assessed energy expenditure, ex vivo muscle contractile performance, and endurance exercise capacity in PDHmKO mice and wild-type (WT) littermates. Additionally, we studied glucose homeostasis and insulin sensitivity in muscle after 12 wk of HFD feeding. TMX administration largely ablated PDHα in skeletal muscle of adult PDHmKO mice but did not impact energy expenditure, muscle contractile function, or low-intensity exercise performance. Additionally, there were no differences in muscle insulin sensitivity or body composition in PDHmKO mice fed a control or HFD, as compared with WT mice. However, exercise capacity during high-intensity exercise was severely impaired in PDHmKO mice, in parallel with a large increase in plasma lactate concentration. In conclusion, although skeletal muscle PDC is not a major contributor to resting energy expenditure or long-duration, low-intensity exercise performance, it is necessary for optimal performance during high-intensity exercise.

The effects of 3 weeks of oral glutathione supplementation on whole body insulin sensitivity in obese males with and without type 2 diabetes: A randomized trial

2021 ◽  
Author(s):  
Stine D. Søndergård ◽  
Ida Cintin ◽  
Anja Birk Kuhlman ◽  
Thomas Morville ◽  
Marie Louise Bergmann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Oxidation Product ◽  
Emission Rate ◽  
Whole Body ◽  
Markers Of Oxidative Stress ◽  
Obese Subjects

The effect of oral glutathione (GSH) supplementation was studied in obese subjects with and without type 2 diabetes (T2DM) on measures of glucose homeostasis and markers of oxidative stress. Twenty subjects (10 patients with T2DM and 10 obese subjects) were recruited for the study, and randomized in a double-blinded placebo-controlled manner to consume either 1000mg GSH per day or placebo for three weeks. Before and after the 3 weeks insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp and a muscle biopsy was obtained to measure GSH and skeletal muscle mitochondrial hydrogen peroxide (H2O2) emission rate. Whole body insulin sensitivity increased significantly in the GSH group. Skeletal muscle GSH was numerically increased (app. 19%) in the GSH group, no change was seen in GSH to glutathione disulfide (GSSG) ratio. Skeletal muscle mitochondrial H2O2 emission rate did not change in response to the intervention and neither did the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine (8-oxoGuo) or the DNA oxidation product 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG ), although 8-oxodG decreased as a main effect of time. Oral GSH supplementation improves insulin sensitivity in obese subjects with and without T2DM, although it does not alter markers of oxidative stress. The study has been registered in clinicaltrials.gov (NCT02948673). Novelty bullets: • Reduced glutathione supplementation increases insulin sensitivity in obese subjects with and without type 2 diabetes • H2O2 emission rate from skeletal muscle mitochondria was not affected by glutathione supplementation

scholarly journals Skeletal muscle-specific overexpression of SIRT1 does not enhance whole-body energy expenditure or insulin sensitivity in young mice

Diabetologia ◽  
2013 ◽  
Vol 56 (7) ◽  
pp. 1629-1637 ◽  
Author(s):  
A. T. White ◽  
C. E. McCurdy ◽  
A. Philp ◽  
D. L. Hamilton ◽  
C. D. Johnson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Whole Body ◽  
Body Energy ◽  
Young Mice

scholarly journals Germline or inducible knockout of p300 or CBP in skeletal muscle does not alter insulin sensitivity

2019 ◽  
Vol 316 (6) ◽  
pp. E1024-E1035 ◽  
Author(s):  
Vitor F. Martins ◽  
Jessica R. Dent ◽  
Kristoffer Svensson ◽  
Shahriar Tahvilian ◽  
Maedha Begur ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Binding Protein ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
High Fat ◽  
Skeletal Muscle Insulin Sensitivity

Akt is a critical mediator of insulin-stimulated glucose uptake in skeletal muscle. The acetyltransferases, E1A binding protein p300 (p300) and cAMP response element-binding protein binding protein (CBP) are phosphorylated and activated by Akt, and p300/CBP can acetylate and inactivate Akt, thus giving rise to a possible Akt-p300/CBP axis. Our objective was to determine the importance of p300 and CBP to skeletal muscle insulin sensitivity. We used Cre-LoxP methodology to generate mice with germline [muscle creatine kinase promoter (P-MCK and C-MCK)] or inducible [tamoxifen-activated, human skeletal actin promoter (P-iHSA and C-iHSA)] knockout of p300 or CBP. A subset of P-MCK and C-MCK mice were switched to a calorie-restriction diet (60% of ad libitum intake) or high-fat diet at 10 wk of age. For P-iHSA and C-iHSA mice, knockout was induced at 10 wk of age. At 13–15 wk of age, we measured whole-body energy expenditure, oral glucose tolerance, and/or ex vivo skeletal muscle insulin sensitivity. Although p300 and CBP protein abundance and mRNA expression were reduced 55%–90% in p300 and CBP knockout mice, there were no genotype differences in energy expenditure or fasting glucose and insulin concentrations. Moreover, neither loss of p300 or CBP impacted oral glucose tolerance or skeletal muscle insulin sensitivity, nor did their loss impact alterations in these parameters in response to a calorie restriction or high-fat diet. Muscle-specific loss of either p300 or CBP, be it germline or in adulthood, does not impact energy expenditure, glucose tolerance, or skeletal muscle insulin action.

scholarly journals Skeletal muscle mitochondrial adaptations induced by long-term cigarette smoke exposure

2021 ◽  
Author(s):  
Stephen T Decker ◽  
Oh Sung Kwon ◽  
Jia Zhao ◽  
John R. Hoidal ◽  
Tomas P. Huecksteadt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Cigarette Smoke ◽  
Muscle Fibers ◽  
Exercise Intolerance ◽  
Oxidative Stress Marker ◽  
Cigarette Smoke Exposure ◽  
Respiratory Capacity ◽  
Permeabilized Muscle ◽  
Mitochondrial Adaptations

Because patients with Chronic Obstructive Pulmonary Disease (COPD) are often physically inactive, it is still unclear whether the lower respiratory capacity in the locomotor muscles of these patients is due to cigarette smoking per se or is secondary to physical deconditioning. Accordingly, the purpose of this study was to examine mitochondrial alterations in the quadriceps muscle of 10 mice exposed to 8-months of cigarette smoke, a sedentary mouse model of emphysema, and 9 control mice, using immunoblotting, spectrophotometry, and high-resolution respirometry in permeabilized muscle fibers. Mice exposed to smoke displayed a two-fold increase in the oxidative stress marker, 4-HNE, (p < 0.05) compared with control mice. This was accompanied by significant decreases in protein expression of UCP3 (65%), ANT (58%), and mitochondrial complexes II-V (~60%-75%). In contrast, maximal ADP-stimulated respiration with complex I and II substrates (CON: 23.6 ± 6.6 and SMO: 19.2 ± 8.2 ρM·mg-1·s-1) or octanoylcarnitine (CON: 21.8 ± 9.0 and SMO: 16.5 ± 6.6 ρM·mg-1·s-1) measured in permeabilized muscle fibers, as well as citrate synthase activity, were not significantly different between groups. Collectively, our findings revealed that mice exposed to cigarette smoke for 8 months, which is typically associated with pulmonary inflammation and emphysema, exhibited a preserved mitochondrial respiratory capacity for various substrates, including free-fatty acid, in the skeletal muscle. However, the mitochondrial adaptations induced by cigarette smoke favored the development of chronic oxidative stress, which can indirectly contribute to augment the susceptibility to muscle fatigue and exercise intolerance.

Both linoleic and α-linolenic acid prevent insulin resistance but have divergent impacts on skeletal muscle mitochondrial bioenergetics in obese Zucker rats

2014 ◽  
Vol 307 (1) ◽  
pp. E102-E114 ◽  
Author(s):  
Sarthak Matravadia ◽  
Eric A. F. Herbst ◽  
Swati S. Jain ◽  
David M. Mutch ◽  
Graham P. Holloway
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Linolenic Acid ◽  
Oxidative Capacity ◽  
Zucker Rats ◽  
Mitochondrial Content ◽  
Beneficial Effects ◽  
Obese Control

The therapeutic use of polyunsaturated fatty acids (PUFA) in preserving insulin sensitivity has gained interest in recent decades; however, the roles of linoleic acid (LA) and α-linolenic acid (ALA) remain poorly understood. We investigated the efficacy of diets enriched with either LA or ALA on attenuating the development of insulin resistance (IR) in obesity. Following a 12-wk intervention, LA and ALA both prevented the shift toward an IR phenotype and maintained muscle-specific insulin sensitivity otherwise lost in obese control animals. The beneficial effects of ALA were independent of changes in skeletal muscle mitochondrial content and oxidative capacity, as obese control and ALA-treated rats showed similar increases in these parameters. However, ALA increased the propensity for mitochondrial H2O2 emission and catalase content within whole muscle and reduced markers of oxidative stress (4-HNE and protein carbonylation). In contrast, LA prevented changes in markers of mitochondrial content, respiratory function, H2O2 emission, and oxidative stress in obese animals, thereby resembling levels seen in lean animals. Together, our data suggest that LA and ALA are efficacious in preventing IR but have divergent impacts on skeletal muscle mitochondrial content and function. Moreover, we propose that LA has value in preserving insulin sensitivity in the development of obesity, thereby challenging the classical view that n-6 PUFAs are detrimental.

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